College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Eur J Pharm Sci. 2010 Jan 31;39(1-3):1-7. doi: 10.1016/j.ejps.2009.05.006. Epub 2009 May 18.
It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. It has also been reported that the protein expression and/or mRNA levels of hepatic CYP2C11, 2D subfamily, and 3A1 have decreased, decreased, and increased, respectively, in U-ARF rats. Thus, pharmacokinetic changes of intravenous metformin in U-ARF rats were evaluated. Metformin was administered intravenously at a dose of 50mg/kg to control and U-ARF rats. After i.v. administration of metformin to U-ARF rats, its time-averaged total body clearance was significantly slower (95.2% decrease) than controls. This could have been due to both significantly slower time-averaged renal clearance (99.1% decrease; due to a urine flow rate-dependent timed-interval renal clearance of the drug, a decrease in renal OCT2, and/or an impaired kidney function in U-ARF rats) and time-averaged non-renal clearance (83.8% decrease; due to a decrease in hepatic CYP2C11 and 2D subfamily in U-ARF rats).
据报道，在大鼠中，二甲双胍主要通过肝 CYP2C11、2D1 和 3A1/2 代谢。也有报道称，U-ARF 大鼠的肝 CYP2C11、2D 亚家族和 3A1 的蛋白表达和/或 mRNA 水平分别降低、降低和增加。因此，评估了 U-ARF 大鼠中静脉内二甲双胍的药代动力学变化。在对照和 U-ARF 大鼠中以 50mg/kg 的剂量静脉给予二甲双胍。在 U-ARF 大鼠中静脉给予二甲双胍后，其平均总清除率明显较慢（降低 95.2%）。这可能是由于平均肾清除率明显较慢（降低 99.1%；由于药物的尿流率依赖性时间间隔肾清除率、肾脏 OCT2 减少和/或 U-ARF 大鼠的肾功能受损）和平均非肾清除率降低（降低 83.8%；由于 U-ARF 大鼠中肝 CYP2C11 和 2D 亚家族减少）。
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